Scavenger receptor-BI localizes to a late endosomal compartment

Malika Ahras, Thet Naing, and Ruth McPherson

Medicine, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7

Corresponding Author: rmcpherson{at}ottawaheart.ca

Scavenger receptor-BI (SR-BI) has an established role in mediating the selective uptake of cholesterol from high density lipoproteins (HDL) in hepatocytes, steroidogenic cells and other tissues. SR-BI is present on the plasma membrane but also localizes to stable intracellular compartments of unknown function. Using indirect immunofluorescence and subcellular fractionation, we have investigated the subcellular distribution of SR-BI. We report that red fluorescent protein (RFP)-tagged mouse SR-BI (RFP-mSRBI) colocalizes with the late endosomal and lysosomal markers, Rab7, LBPA and Rab9. In addition, endogenous SR-BI is also found on lysosomes and colocalises with LAMP-2 in primary hepatocytes. Furthermore, we demonstrate that the trafficking of SR-BI through these compartments is Rab7-dependent. Interestingly, filipin staining indicates accumulation of lysosomal cholesterol in SR-BI deficient (-/-) as compared to wild type hepatocytes. In addition to its role as a plasma membrane receptor, SR-BI may function in cholesterol trafficking from late endosomes/lysosomes.

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